Effort Of Ezetimibe And Rosuvastatin On Expression Of LXR?-ABCA1 Genes And Proteins In Foam Cells Derived From Vascular Smooth Muscle

Objective:To explore the effect of ezetimibe and rosuvastatin used alone or in combination on the expression of liver X receptor alpha(LXR?)and ATP binding cassette transporter A1(ABCA1)in foam cells derived from vascular smooth muscle cells(VSMCs),to observe whether the two drugs can reduce the cholesterol content of foam cells via LXR alpha-ABCA1 pathway,and whether they can reduce cholesterol accumulation more effectively in combination,so as to play an anti atherosclerosis effect.Methods:The normal rat aortic smooth muscle cells(VSMCs)were taken as the blank control group.The VAMCs were converted to foam cells using OX-LDL(50ug/mL),According to the experimental requirements,the smooth muscle were devided into blank control group,foam cells group,different concentrations of ezetimibe groups(3umol/L,10umol/L and 30umol/L),rosuvastatin group(0.1umol/L,1umol/l,5umol/l)and combined group(30umol/L ezetimibe + 5 umol/L rosuvastatin).Oil red O staining identification foam cell model,Real-time PCR was used to detect the mRNA levels of LXR? and ABCA1 in each groups,as well as the protein levels were detected by Western blot.The contents of total cholesterol(TC)and free cholesterol(FC)in each groups were detected by Enzyme Fluorescence method.Result:1.The effect of ezetimibe and rosuvastatin on the mRNA expressions of LXR?,ABCA1:Compared with the blank control group,the mRNA expressions of LXR? and ABCA1 decreased significantly in OX-LDL group(P<0.01);Compared with OX-LDL group,the mRNA expressions of LXR? and ABCA1 were upregulated by different concentrations of ezetimibe and rosuvastatin in a concentration-dependent manner(P<0.01).2.The effect of ezetimibe combined with rosuvastatin on the mRNA and protein expressions of LXR?,ABCA1:Compared with blank control group,the mRNA and protein expressions of LXR?,ABCA1 was decreased significantly(P<0.01);Compared with OX-LDL group,the mRNA and protein expressions of LXR?,ABCA1 were increased in ezetimibe group(30umol/l),rosuvstatin group(5umol/l)and combined group(P<0.01);Compared with the single drug group,the mRNA and protein expressions of LXR?,ABCA1 were further increased in combination group(P<0.01);3.The effect of ezetimibe combined with rosuvastatin on intracellular cholesterol content:Compared with the blank control group,the contents of the Total cholesterol,free cholesterol,cholesterol ester were increased significantly in OX-LDL group(P<0.01);Compared with OX-LDL group,the contents of all kinds of cholesterol were decreased in ezetimibe group,rosuvastatin group and combination group(P<0.01);Compared with the single drug group,tthe contents of all kinds of cholesterol were fuether decreased in combinatation group(P<0.01).Conclusions:Ezetimibe and rosuvastatin can via the LXR alpha-ABCA1 pathway,thereby reducing the intracellular cholesterol contents,and both the optimal concentration combination,LXR alpha,ABCA1 expressions were further up-regulated,intracellular cholesterol content were further decreased,resulting in more effective anti atherosclerosis effect.